Throughout this application various publications, including patents and patent application publications, are referred to by publication number or by a number in square brackets. Full citations for the numbered publications may be found at the end of the specification. The disclosures of each of the publications, patents and patent application publications referred to herein are hereby incorporated by reference in their entirety into the subject application to more fully describe the art to which the subject invention pertains.
Fibrosis of the liver is a widely spread disorder which may be caused by any chronic liver disease. It is a wound healing response comprising reversible scarring that occurs in almost all patients with chronic, but not self-limited liver injury. Ultimately, hepatic fibrosis leads to cirrhosis, characterized by nodule formation and organ contraction. In all circumstances, the composition of the hepatic scar is similar. Moreover, the cells and soluble factors participating in this response in liver are also similar to those participating in parenchymal injury to kidney, lung, or skin.
Fibrosis occurs earliest in regions where injury is most severe. In response to liver injury, hepatic stellate cells undergo an “activation” process in which they lose vitamin A, become highly proliferative, and synthesize “fibrotic” matrix rich in type I collagen, and fibrosis ensues. No effective treatments currently exist.
The present invention address the need for targeted treatments for reversal of fibrosis in a tissue, including fibrosis of the liver.